From the state of the art, detection processes with analytes by means of fluorochromes, enzymes or radioactive particles as so called markers for analytes are known. It is a drawback that the linear detection range of fluorescent markers or the sensitivity of enzymatic techniques are limited. Radioactive markers are problematical because of the need to provide radiation protection.
Bioassays on the basis of magnetic marking of analytes is therefore one alternative. The magnetic particles are comprised of an iron oxide core with a defined diameter of several tens of nanometers to several hundred nanometers. They have a biocompatible surface coating with which they can bond to the analytes, for example, to chemical substances, or to the surfaces of cells or viruses in a manner known per se.
Advantageously, such markers are stable, nontoxic and manipulatable by means of magnetic fields. Particles of iron oxide are superparamagnetic. The presence of magnetic particles in a sample volume can be determined by alternating field susceptometry. In the case of monodispersitates, i.e. a unitary particle size, the concentration of the particles can also be quantitatively determined.
From U.S. Pat. No. 6,110,660 the detection of magnetic particles by means of susceptometry is known. In that case the magnetic susceptibility of an analyte is measured by means of a Maxwell bridge in the frequency range around 200 kHz. The measured electrical voltage on an output amplifier of the bridge is proportional to the susceptability of the solution. With constant particle size, the susceptibility is also proportional to the number of magnetic particles in solution.
The drawback is that this method is not selective. Indeed the magnetic susceptibility of concentrated nanoparticle solutions is high. However, immunoassay methods as a rule detect very small concentrations of biomolecules and consequently very small concentrations of magnetic marker particles. The resulting susceptibility of the solution is then very small and can hardly be distinguished from the susceptibility of a control solution or blank without magnetic particles. To increase the amplification at the output of the Maxwell bridge is hardly a usable solution to this problem because of parasitic effects like susceptibility variations in the sample vessel, the reagents and the laboratory environment as well as the spread in the output voltage give rise like thermal effects and electrical drifting of the components of the readout circuit interfere.
From U.S. Pat. No. 6,046,585, the movement of magnetic particle samples to produce a low frequency modulation of the measurement signal using a qradiometric SQUID magnetic field detector is known. The drawback here is that signals from the sample holder and the sample vessel cannot be suppressed in this process.